This proposal for a Mentored Clinical Scientist Research Career Development Award describes the career goals, career development plan and research strategy for Dr. Brian Campfield, Assistant Professor of Pediatrics at the University Of Pittsburgh School Of Medicine. Dr. Campfield obtained his M.D. from the University Of Pittsburgh School Of Medicine, and completed his Pediatric and Pediatric Infectious Diseases training at the Children's Hospital of Pittsburgh. This proposal builds upon the novel observation that Follistatin- like protein 1 (FSTL-1) plays a critical role in lung homeostasis by inhibiting inflammation and protease activity that results in emphysema. Emphysema is a common component of COPD, which is the 3rd leading cause of mortality in the world accounting for an estimated cost of $50 billion in the U.S. The mortality, incidence and cost of COPD continue to increase arguing that improved preventative, diagnostic and therapeutic modalities are urgently needed. Our current understanding of the pathophysiology is incomplete and many current preclinical models have limited ability to reproduce the complex pathophysiology of human emphysema. Dr. Campfield's research program has observed that a global, conditional FSTL-1 knockout mouse spontaneously develops emphysema, and this phenotype is associated specifically with increased Type 17 cytokines, increased matrix metalloproteinase expression and excessive protease activity in the lung. Additionally, using computed tomography they are able to identify emphysematous changes that will allow for the study individual animals longitudinally. Dr. Campfield hypothesizes that FSTL-1 is critical for normal lung homeostasis such that loss of FSTL-1 results in emphysema. Specifically, FSTL-1 directly limits the recruitment of IL-17 producing cells that drive expression of CCR2 and IL17R ligands in the lung, and FSTL-1 lessens the recruitment of MMP12 expressing macrophages that contribute to the development of emphysema. This hypothesis will be tested along three aims: 1) determine the temporospatial expression of FSTL-1 in the lung and effect of fstl1 conditional knock-out (CKO) at various postnatal time points, 2) determine the requirement of IL-17 receptor and C-C chemokine receptor 2 signaling in emphysema development using the FSTL-1 CKO, and 3) determine role of the lung intrinsic fstl1 expression versus circulating FSTL-1 in preventing the development of emphysema. Dr. Campfield has a Career Development Plan built upon several pillars: rigorous experimental studies; formal academic coursework; high-quality literature, grant and journal review; face-to-face training in the responsible conduct of research; institutional academic development and grant-writing workshops. His research mentorship will primarily come from Dr. Jay Kolls, an outstanding NIH-funded pulmonologist whose pioneering studies have helped define the role of IL-17 in immunity and inflammation in the lung. Dr. Campfield will also receive guidance by a Scholarship Mentoring Committee comprised of three successful physician- scientists as he executes this proposal and transitions to a career as an independent investigator.